Analyses of lung cancer-derived volatiles in exhaled breath and in vitro models

Abstract

Lung cancer is one of the leading causes of cancer incidence and cancer-related deaths in the world. Early diagnosis of pulmonary tumors results in improved survival compared to diagnosis with more advanced disease, yet early disease is not reliably indicated by symptoms. Despite of the improved testing and monitoring techniques for lung cancer in the past decades, most diagnostic tests, such as sputum cytology or tissue biopsies, are invasive and risky, rendering them unfeasible for large population screening. The non-invasive analysis of exhaled breath has gained attentions as an innovative screening method to measure chemical alterations within the human volatilome profile as a result of oncogenesis. More importantly, volatile organic compounds (VOCs) have been correlated to the pathophysiology of disease since the source of volatile compounds relies mostly on endogenous metabolic processes that are altered as a result of disease onset. Therefore, studying VOCs emitted from human breath may assist lung cancer diagnosis, treatment monitoring, and other surveillance of this devastating disease. In this mini review, we evaluated recent human studies that have attempted to identify lung cancer-derived volatiles in exhaled breath of patients. We also examined reported volatiles in cell cultures of lung cancer to better understand the origins of cancer-associated VOCs. We highlight the metabolic processes of lung cancer that could be responsible for the endogenous synthesis of these VOCs and pinpoint the protein-encoding genes involved in these pathways. Finally, we highlight the potential value of a breath test in lung cancer and propose prominent areas for future research required for the incorporation of VOCs-based testing into clinical settings.

Progress and challenges of developing volatile metabolites from exhaled breath as a biomarker platform

“…In particular, the process of lipid peroxidation producing specific aldehydes, especially pentanal, hexanal, and heptanal, have been raised as repeatably represented across the literature in breath VOC profiles of those with lung cancer (Sutaria et al, 2022 ). However, despite the large amount of work in this area, there are currently no clinically validated breath biomarkers or tests suitable for lung cancer screening due to historical issues with standardization (Antoniou et al, 2019 ; Choueiry et al, 2022 ; Keogh & Riches, 2022 ).…”

Non-Invasive Lung Cancer Diagnostics through Metabolites in Exhaled Breath: Influence of the Disease Variability and Comorbidities

“…Lung cancer biomarkers can be identified using various analytical methods [ 11 , 12 ]. Among them, gas chromatography coupled with mass spectrometry (GC-MS) is extremely useful since it allows to conduct quantitative and qualitative analysis of the samples.…”